BILIRUBIN AS A MARKER OF OXIDATIVE STRESS AND NON-COMMUNICABLE DISEASE: CHICKEN OR THE EGG?

Abstract

Oxidative stress has been implicated in most non-communicable diseases: that is, metabolic syndrome (MetS), atherosclerosis and cancer. LDL cholesterol is rendered more atherogenic by oxidative modification [1] and many carcinogens create free oxygen radicals that damage DNA and other cellular structures, initiating and promoting tumor development [2]. Therefore, antioxidant agents have been extensively evaluated in the prevention of cardiovascular disease and cancer.Vitamin E has been shown to reduce atherosclerotic lesions in animals [3], smooth muscle cell proliferation [4], platelet adherence and aggregation [5]. Epidemiological data indicate an inverse association between cardiovascular or cancer risk and vitamin E intake from dietary sources and/or supplements [6]. However, most randomized controlled trials have failed to confirm a role for vitamin E supplementation in cardiovascular prevention [7-11]. Vitamin E had no significant effect on myocardial infarction, stroke, cardiovascular death, unstable angina, revascularization, and total mortality.Trials of cancer chemoprevention have also been disappointing [12, 13].

 Bilirubin has been recognized as a potent antioxidant. Bilirubin suppresses the oxidation of lipid in liposomes more than vitamin E, which is regarded as the best antioxidant of lipid peroxidation [14, 15]. The water-soluble glutathione primarily protects water soluble proteins, whereas the lipophilic bilirubin protects lipids from oxidation [16]. Serum bilirubin has been demonstrated to be a major contributor to the total antioxidant capacity in blood plasma [17] and proven to haveanti-inflammatory properties [18]. Serum bilirubin was shown to be cross-sectionaly associated with MetS in Chinese children, adolescents and adults [19, 20] as well as Korean men and women [21, 22]. Patients with Gilbert syndrome had low levels of oxidative stress associated with enhancement of endothelium-dependent vasodilation [23].Serum bilirubin has been demonstrated to be negatively associated with cardiovascular disease [24-26], hemoglobin A1c [27] and albuminuria [28]. The authorpreviously suggested that serum bilirubin might be a negative predictor of end-stage kidney disease [29].Others reported that serum bilirubin predicted MetS [30, 31]. However, the author demonstrated that serum bilirubin cannot predict the development of MetS and suggested that a decreased serum bilirubin was not a cause of MetS but a marker of oxidative stress [32] which is closely related to inflammation [18] and endothelial dysfunction [23], both of which are thought to be underlying mechanisms of MetS [33].So, further prospective studies are required to conclude whether a decrease in serum bilirubin is a risk factor of non-communicable disease such as MetS [34].

 

Acknowledgments

The author received no financial support and has no conflict of interest.